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We discuss how host restriction factors have shaped the emergence of new SIV zoonoses by imposing adaptive hurdles to cross-species transmission and/or secondary spread.We also show that AIDS has likely afflicted chimpanzees long before the emergence of HIV.A retrovirus, now termed human immunodeficiency virus type 1 (HIV-1), was subsequently identified as the causative agent of what has since become one of the most devastating infectious diseases to have emerged in recent history (Barre-Sinoussi et al. Although antiretroviral treatment has reduced the toll of AIDS- related deaths, access to therapy is not universal, and the prospects of curative treatments and an effective vaccine are uncertain (Barouch 2008; Richman et al. Thus, AIDS will continue to pose a significant public health threat for decades to come. These relationships provided the first evidence that AIDS had emerged in both humans and macaques as a consequence of cross-species infections with lentiviruses from different primate species (Sharp et al. Indeed, subsequent studies confirmed that SIVmac was not a natural pathogen of macaques (which are Asian primates), but had been generated inadvertently in US primate centers by inoculating various species of macaques with blood and/or tissues from naturally infected sooty mangabeys (Apetrei et al. Similarly, it became clear that HIV-1 and HIV-2 were the result of zoonotic transfers of viruses infecting primates in Africa (Hahn et al. In this article, we summarize what is known about the simian precursors of HIV-1 and HIV-2, and retrace the steps that led to the AIDS pandemic. Old World monkeys are naturally infected with more than 40 different lentiviruses, termed simian immunodeficiency viruses (SIVs) with a suffix to denote their primate species of origin (e.g., SIVsmm from sooty mangabeys).Ever since HIV-1 was first discovered, the reasons for its sudden emergence, epidemic spread, and unique pathogenicity have been a subject of intense study. Soon thereafter, additional viruses, collectively termed simian immunodeficiency viruses (SIVs) with a suffix to denote their species of origin, were found in various different primates from sub-Saharan Africa, including African green monkeys, sooty mangabeys, mandrills, chimpanzees, and others (Fig. Surprisingly, these viruses appeared to be largely nonpathogenic in their natural hosts, despite clustering together with the human and simian AIDS viruses in a single phylogenetic lineage within the radiation of lentiviruses (Fig. Interestingly, close simian relatives of HIV-1 and HIV-2 were found in chimpanzees (Huet et al. Several of these SIVs have crossed the species barrier to great apes and humans, generating new pathogens (see text for details).Here, we describe the origins and evolution of these viruses, and the circumstances that led to the AIDS pandemic.Both HIVs are the result of multiple cross-species transmissions of simian immunodeficiency viruses (SIVs) naturally infecting African primates.[When Natalie Wood began dating Warren Beatty] I wanted to kill that son of a bitch...I was hanging around outside his house with a gun, hoping he would walk out.

Figure 3A summarizes current molecular epidemiological data derived from the analysis of over 7,000 chimpanzee fecal samples collected at nearly 90 field sites (Santiago et al. The upper panel depicts the ranges of the four subspecies of the common chimpanzee (, brown) gorillas (map courtesy of Lilian Pintea, The Jane Goodall Institute). Moreover, there is no evidence that chimpanzees harbor any other SIV, although they, as well as bonobos, are routinely exposed to SIVs through their hunting behavior (Mitani and Watts 1999; Surbeck and Hohmann 2008; Leendertz et al. Initially, SIVcpz was thought to be harmless for its natural host.

Data were compiled from several studies (Santiago et al. This was because none of the few captive apes that were naturally SIVcpz infected suffered from overt immunodeficiency, although in retrospect this conclusion was based on the immunological and virological analyses of only a single naturally infected chimpanzee (Heeney et al. In addition, SIV-infected sooty mangabeys and African green monkeys showed no sign of disease despite high viral loads in blood and lymphatic tissues (Paiardini et al.

2009), leading to the belief that all naturally occurring SIV infections are nonpathogenic.

This host-specific clustering indicates that the great majority of transmissions occur among members of the same species; however, there are also numerous documented instances when SIVs have crossed between species. Thus, it is clear that in addition to more long-standing virus/host relationships, a number of naturally occurring SIVs have emerged more recently as a result of cross-species transmission and recombination.

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